FXR2P Exerts a Positive Translational Control and Is Required for the Activity-Dependent Increase of PSD95 Expression
- Esperanza Fernández1,2,
- Ka Wan Li3,
- Nicholas Rajan1,2,
- Silvia De Rubeis1,2,
- Mark Fiers1,2,
- August B. Smit3,
- Tilmann Achsel1,2, and
- Claudia Bagni1,2,4
- 1KU Leuven, Center for Human Genetics and Leuven Institute for Neuroscience and Disease, Leuven, Belgium,
- 2VIB Center for the Biology of Disease, 3000 Leuven, Belgium,
- 3Department of Molecular and Cellular Neurobiology, Center for Neurogenomics and Cognitive Research, Neuroscience Campus Amsterdam, VU University Amsterdam, 1081 HV Amsterdam, The Netherlands, and
- 4University of Rome Tor Vergata, Department of Biomedicine and Prevention, 00133 Rome, Italy
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Author contributions: E.F., K.W.L., A.B.S., T.A., and C.B. designed research; E.F., K.W.L., N.R., and S.D.R. performed research; E.F., K.W.L., N.R., S.D.R., M.F., A.B.S., T.A., and C.B. analyzed data; E.F., T.A., and C.B. wrote the paper.
Abstract
In brain, specific RNA-binding proteins (RBPs) associate with localized mRNAs and function as regulators of protein synthesis at synapses exerting an indirect control on neuronal activity. Thus, the Fragile X Mental Retardation protein (FMRP) regulates expression of the scaffolding postsynaptic density protein PSD95, but the mode of control appears to be different from other FMRP target mRNAs. Here, we show that the fragile X mental retardation-related protein 2 (FXR2P) cooperates with FMRP in binding to the 3′-UTR of mouse PSD95/Dlg4 mRNA. Absence of FXR2P leads to decreased translation of PSD95/Dlg4 mRNA in the hippocampus, implying a role for FXR2P as translation activator. Remarkably, mGluR-dependent increase of PSD95 synthesis is abolished in neurons lacking Fxr2. Together, these findings show a coordinated regulation of PSD95/Dlg4 mRNA by FMRP and FXR2P that ultimately affects its fine-tuning during synaptic activity.
- Received November 20, 2014.
- Revision received May 10, 2015.
- Accepted May 11, 2015.
- Copyright © 2015 the authors 0270-6474/15/359402-07$15.00/0
